LONDON — A cure for pancreatic cancer may be one step closer after the discovery of a protein that fuels the disease’s spread. Researchers in London found that manipulating levels of the protein reverses the ability of tumors to change into a more aggressive form.
The disease is one of the world’s deadliest forms of cancer. It has the worst survival rates in comparison to other common cancers, with only one in 20 patients living longer than five years after diagnosis.
More effective therapies are in desperate need. The study in the journal Nature opens the door to developing drugs that target a gene called GREM1.
Switching off pancreatic cancer before it spreads?
Switching the gene off led tumor cells to rapidly change shape and develop new properties that helped them migrate around the body. They all turned into a dangerous, invasive type within 10 days. Researchers used lab rodents and mini tumors (organoids) grown in petri dishes during their experiments.
The British team studied a mouse model of pancreatic ductal adenocarcinoma (PDAC), which is the most common and lethal variety. Around 90 percent of animals without functioning GREM1 developed tumors which had spread to their liver — compared to 15 percent where the gene was working normally.
Boosting levels of the protein reversed the process, causing invasive cells to revert into a less dangerous form. This breakthrough could lead to the development of drugs that makes advanced pancreatic cancer easier to treat. Fundamental discoveries such as this are crucial in directing efforts to find new cancer drugs and treatments.
“This is an important and fundamental discovery that opens up a new avenue for uncovering treatments for pancreatic cancer,” says senior author Professor Axel Behrens from The Institute of Cancer Research, in a media release.
“We have shown that it is possible to reverse cell fate in pancreatic cancer in the lab – turning back the clock on aggressive tumors and switching them to a state that makes them easier to treat.”
“By better understanding what drives the aggressive spread of pancreatic cancer, we hope to now exploit this knowledge and identify ways to make pancreatic cancer less aggressive, and more treatable.”
What makes the disease so hard to treat?
The American Cancer Society estimates that roughly 62,210 people will receive a pancreatic cancer diagnosis this year. The study in Nature also showed another protein, BMP2, regulates GREM1.
The two proteins regulate the form PDAC cells ultimately take — a mathematical model first proposed by World War II codebreaker Alan Turing in 1952. These “Turing patterns” are found in nature, from the skin of the giant puffer fish to seashells.
Strikingly, the same sort of design is present in the different types of cells found in pancreatic cancer. It could also apply to other forms of the disease as well.
“Pancreatic cancer is one of the most devastating of all cancers – the most common form of the disease spreads aggressively, making it hard-to-treat and a terrifying diagnosis for patients and their loved ones,” says Prof. Kristian Helin, chief executive of The Institute of Cancer Research.
“This new finding has broadened our understanding of the molecular basis of how pancreatic cancer gains the ability to grow and spread around the body. Although more work is required, this type of fundamental research is essential for developing concepts for new and more effective treatments for cancer.”
Pancreatic cancer is notoriously difficult to treat. Patients tend to be diagnosed in the later stages of the disease due to there being no screening program and the symptoms generally being vague, like upper abdominal pain. The pancreas is also situated near other vital organs, like the liver and intestines, raising the risk a tumor will spread.
South West News Service writer Mark Waghorn contributed to this report.
